1. Fuerst, Mark L.

Article Content

SAN FRANCISCO-Patient-reported outcome (PRO) measures show newer drug combinations not only improve survival, but lead to improvements in quality of life in unresectable hepatocellular carcinoma (HCC) and a specific type of colorectal cancer (CRC), according to extended results of two studies presented at the ASCO 2020 Gastrointestinal Cancers Symposium.

Colorectal  Liver Ca... - Click to enlarge in new windowColorectal & Liver Cancers. Colorectal & Liver Cancers

In one study, the combination of atezolizumab plus bevacizumab delayed declines in quality of life compared to a two-drug treatment with sorafenib (the standard of care) for patients with unresectable HCC. In the second study, patients with metastatic CRC that has a BRAF V600E mutation treated with encorafenib and cetuximab with or without binimetinib were able to maintain their quality of life longer than those treated with one of two standard-of-care regimens.


Unresected HCC

The combination of atezolizumab, a programmed cell death-ligand 1 inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, has proved successful in unresected HCC in terms of improving survival and quality of life.


"Because it reflects both the effects of disease and the side effects of treatment, sustained or improved quality of life is particularly important for patients," said lead author Peter R. Galle, MD, PhD, of the University Medical Center in Mainz, Germany. "Patients with liver cancer are typically more fragile and frail than others. Toxicity of the treatments can be much more serious for these patients, and their quality of life can decline quite quickly."


The phase III IMbrave 150 trial compared atezolizumab plus bevacizumab with sorafenib alone as a first-line treatment for patients with HCC who had not received prior systemic therapy. The primary endpoint of overall survival was presented at the ESMO Asia Congress in November 2019. At that time, median overall survival had not yet been reached for atezolizumab plus bevacizumab compared with overall survival of 13.2 months for patients receiving sorafenib alone. The overall response rate was 27 percent with atezolizumab plus bevacizumab and 12 percent for sorafenib.


At the ASCO Gastrointestinal Cancers Symposium, Galle presented PRO results from the study (Abstract 476). Time to deterioration, assessed by two validated patient-reported quality of life tools, was a pre-specified secondary endpoint of the study. Time to deterioration was defined as a decrease of 10 points from baseline in key PROs. At baseline, every 3 weeks during therapy, and every 3 months after discontinuation of therapy, patients completed two questionnaires (one specific to HCC) to assess quality of life, physical functioning, and role functioning. Questionnaire completion rates were about 92 percent, he noted.


Time to deterioration was a median of 11.2 months for the combination treatment compared with 3.6 months for sorafenib. Declines in physical functioning were also delayed with the combination treatment, with a median delay of 13.1 months with atezolizumab and bevacizumab compared with 4.9 months for sorafenib.


In conclusion, Galle said: "High-quality PRO results from IMbrave 150 showed large and consistent benefits in key aspects of the patient experience with atezolizumab plus bevacizumab, further supporting its overall clinical benefit in patients with unresectable HCC who have not received prior systemic therapy."


Metastatic CRC With Mutated BRAF V600E

In the BEACON CRC study, an open-label, 3-arm, phase III global study, the triplet regimen of encorafenib plus binimetinib plus cetuximab significantly improved overall survival and objective response rates in 665 patients with BRAF V600E metastatic CRC compared with current standard of care. The standard of care regimens consisted of irinotecan plus cetuximab or FOLFIRI (leucovorin, calcium folinate, fluorouracil, and irinotecan) with cetuximab.


At the Gastrointestinal Cancers Symposium, lead author Scott Kopetz, MD, PhD, Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, reported on patients' quality of life, which was a secondary endpoint of the study (Abstract 8). Quality of life was assessed at baseline and after every treatment cycle using four validated measurement tools. In particular, the researchers looked at the time to 10 percent or greater deterioration between the study arms, which is considered to represent a clinically meaningful decline in quality of life.


Patients treated with the triplet had a roughly 44-45 percent reduction in the risk of quality-of-life deterioration compared with patients in the standard-of-care group, based on two of the measures. Those receiving the doublet had a roughly 46 percent reduction in risk. There was no significant difference in quality of life for patients in the triplet and doublet groups.


"The findings highlight that with these novel targeted therapy regimens, not only was disease controlled longer, but patient-reported quality of life was maintained longer," said Kopetz. He noted that the BRAF V600E mutation occurs in about 10 percent of CRC patients and has a poor prognosis.


In conclusion, Kopetz said: "In the BEACON CRC study, triplet and doublet regimens demonstrated substantial improvement in patient-reported quality-of-life assessments over the current standard of care in patients with BRAF V600E-mutant metastatic CRC whose disease had progressed after 1 or 2 prior regimens."


Richard L. Schilsky, MD, ASCO Chief Medical Officer and Executive Vice President, commented: "PROs are now recognized as important endpoints of cancer clinical trials that provide important insights regarding the impact of treatment on patients' quality of life. PROs inform us about the tolerability of new therapies, which is just as important as efficacy in gauging their utility and acceptance by patients. There is also evidence that suggests that PROs can have prognostic value for cancer patients. As we get better at including quality-of-life measures in clinical trials, we will continue to see the importance of patient reports grow."


Mark L. Fuerst is a contributing writer.